MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function

Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor_biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions

The conservation impacts of ecological disturbance : time-bound estimates of population loss and recovery for fauna affected by the 2019–2020 Australian megafires

Aim: After environmental disasters, species with large population losses may need urgent protection to prevent extinction and support recovery. Following the 2019–2020 Australian megafires, we estimated population losses and recovery in fire-affected fauna, to inform conservation status assessments and management. Location: Temperate and subtropical Australia. Time period: 2019–2030 and beyond. Major taxa: Australian terrestrial and freshwater vertebrates; one invertebrate group. Methods: From > 1,050 fire-affected taxa, we selected 173 whose distributions substantially overlapped the fire extent. We estimated the proportion of each taxon’s distribution affected by fires, using fire severity and aquatic impact mapping, and new distribution mapping. Using expert elicitation informed by evidence of responses to previous wildfires, we estimated local population responses to fires of varying severity. We combined the spatial and elicitation data to estimate overall population loss and recovery trajectories, and thus indicate potential eligibility for listing as threatened, or uplisting, under Australian legislation. Results: We estimate that the 2019–2020 Australian megafires caused, or contributed to, population declines that make 70–82 taxa eligible for listing as threatened; and another 21–27 taxa eligible for uplisting. If so-listed, this represents a 22–26% increase in Australian statutory lists of threatened terrestrial and freshwater vertebrates and spiny crayfish, and uplisting for 8–10% of threatened taxa. Such changes would cause an abrupt worsening of underlying trajectories in vertebrates, as measured by Red List Indices. We predict that 54–88% of 173 assessed taxa will not recover to pre-fire population size within 10 years/three generations. Main conclusions: We suggest the 2019–2020 Australian megafires have worsened the conservation prospects for many species. Of the 91 taxa recommended for listing/uplisting consideration, 84 are now under formal review through national processes. Improving predictions about taxon vulnerability with empirical data on population responses, reducing the likelihood of future catastrophic events and mitigating their impacts on biodiversity, are critical. © 2022 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Diana Kuchinke” is provided in this record*

What do you mean, ‘megafire’?

BACKGROUND : ‘Megafire’ is an emerging concept commonly used to describe fires that are extreme in terms of size, behaviour, and/or impacts, but the term’s meaning remains ambiguous. APPROACH : We sought to resolve ambiguity surrounding the meaning of ‘megafire’ by conducting a structured review of the use and definition of the term in several languages in the peer-reviewed scientific literature. We collated definitions and descriptions of megafire and identified criteria frequently invoked to define megafire. We recorded the size and location of megafires and mapped them to reveal global variation in the size of fires described as megafires. RESULTS : We identified 109 studies that define the term ‘megafire’ or identify a megafire, with the term first appearing in the peer-reviewed literature in 2005. Seventy-one (~65%) of these studies attempted to describe or define the term. There was considerable variability in the criteria used to define megafire, although definitions of megafire based on fire size were most common. Megafire size thresholds varied geographically from > 100–100,000 ha, with fires > 10,000 ha the most common size threshold (41%, 18/44 studies). Definitions of megafire were most common from studies led by authors from North America (52%, 37/71). We recorded 137 instances from 84 studies where fires were reported as megafires, the vast majority (94%, 129/137) of which exceed 10,000 ha in size. Megafires occurred in a range of biomes, but were most frequently described in forested biomes (112/137, 82%), and usually described single ignition fires (59% 81/137). CONCLUSION : As Earth’s climate and ecosystems change, it is important that scientists can communicate trends in the occurrence of larger and more extreme fires with clarity. To overcome ambiguity, we suggest a definition of megafire as fires > 10,000 ha arising from single or multiple related ignition events. We introduce two additional terms – gigafire (> 100,000 ha) and terafire (> 1,000,000 ha) – for fires of an even larger scale than megafires.DATA AVAILABILITY STATEMENT: A list of the references from which the data were extracted can be found in the Appendix A: Data sources. The data used in this study are openly available at zenodo.org: https://doi.org/10.5281/zenodo.6252145.Threatened Species Recovery Hub; NSW Bushfire Risk Management Research Hub; Australian Wildlife Society; World Wildlife Fund.http://wileyonlinelibrary.com/journal/gebZoology and Entomolog

Molecular genetic analysis of male tail development in C. elegans

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After the bushfires, we helped choose the animals and plants in most need : here's how we did it

No other event in our lifetimes has brought such sudden, drastic loss to Australia’s biodiversity as the last bushfire season. Governments, researchers and conservationists have committed to the long road to recovery. But in those vast burnt landscapes, where do we start? We are among the wildlife experts advising the federal government on bushfire recovery. Our role is to help determine the actions needed to stave off extinctions and help nature recover in the months and years ahead. Our first step was to systematically determine which plant and animal species and ecosystems needed help most urgently. So let’s take a closer look at how we went about it

Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability.

Funder: Blood Cancer UK/Grant Number 16001The ETV6-RUNX1 onco-fusion arises in utero, initiating a clinically silent pre-leukemic state associated with the development of pediatric B-acute lymphoblastic leukemia (B-ALL). We characterize the ETV6-RUNX1 regulome by integrating chromatin immunoprecipitation- and RNA-sequencing and show that ETV6-RUNX1 functions primarily through competition for RUNX1 binding sites and transcriptional repression. In pre-leukemia, this results in ETV6-RUNX1 antagonization of cell cycle regulation by RUNX1 as evidenced by mass cytometry analysis of B-lineage cells derived from ETV6-RUNX1 knock-in human pluripotent stem cells. In frank leukemia, knockdown of RUNX1 or its co-factor CBFβ results in cell death suggesting sustained requirement for RUNX1 activity which is recapitulated by chemical perturbation using an allosteric CBFβ-inhibitor. Strikingly, we show that RUNX1 addiction extends to other genetic subtypes of pediatric B-ALL and also adult disease. Importantly, inhibition of RUNX1 activity spares normal hematopoiesis. Our results suggest that chemical intervention in the RUNX1 program may provide a therapeutic opportunity in ALL

MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function.

From PubMed via Jisc Publications RouterHistory: received 2020-06-01, accepted 2021-03-19Publication status: ppublishFunder: Wellcome Trust; Grant(s): 204394Funder: British Heart Foundation; Grant(s): PG/12/36/29444Funder: Medical Research Council; Grant(s): MR/M003493/1, MR/R024812/1Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor-biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, and expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions. [Abstract copyright: Copyright © 2021 The Authors.